Studies On Enteric Coating Of Solid Lipid Nanoparticles

Oral delivery is one of the most widely used traditional drug administration route at present as it is safe,and convenient which can improve the patient's compliance and be of low cost of production.However,some active drugs are unstable,easy to decompose,not easy to be absorbed in the gastrointestinal tract,and has low solubility in gastric acid.And part of them will cause damage to the gastrointestinal tract.Thus,this research is aimed to find out a carrier which can protect not only the drugs,but also the gastrointestinal tract.In previous study,solid lipid nanoparticles have great potential due to its good biocompatibility,stability and controlibility.Yet,solid lipid nanocarrier will be eroded by enzymes in stomach,which results in drug leakage,and aggregation of nanoparticles in gastric juice.This makes it difficult for nanoparticles to spread again and not conducive to subsequent absorption.Therefore,solid lipid nanoparticles were coated with enteric materials to protect them from damage of gastric acid,and enable it disperse homogeneously in intestinal juice and finally improve the absorption.In this study,glycerol monostearate was used to preparesolid lipid nanoparticles by solvent diffusion method with EUDRAGIT(?)L100 as coating material and castor oil as plasticizer.Enteric coating meterial and plasticizer were dissolved in anhydrous ethanol to coat solid lipid nanoparticles by solvent duffusion.And the nanoparticles powder was obtain by spray drying method with curing in 40? oven for 24 h.Simvastatin was used as model drug in the preparation of enteric coating simvastatin solid lipid nanoparticle.The zeta potential and particle size were-22.83 mV and 221.23 nm,and the encapsulation rate was 96.81%.Its shape observed by transmission electron microscopy(SEM)is spherically round and its particle size is homogeneous.After placing in artificial gastric juice(i.e.0.1 mol/ml of hydrochloric acid)for 2 h,enteric coating nanoparticles and ordinary nanoparticles both precipitate flocculently.To deal with the artificial intestinal juice(i.e.0.2 mol/ml sodium phosphate-0.1 mol/ml hydrochloric acid = 1:3,pH = 6.8)for 45 min,enteric coating nanoparticles spread quickly in a short time while ordinary nanoparticles is still the floccule gathered as large particles.After the drug release reached equilibrium,precipitation and suspended particles were still visible in the ordinary nanoparticles,while enteric coating nanoparticles were evenly dispersed.Compared with ordinary nanoparticles,the release results showed that the enteric-coated nanoparticles had less leakage in the artificial gastric juice,and the cumulative release rate of the drug was higher after the drug release reached equilibrium.It can be learned that the coating layer has protective effect on the nanoparticles in the acid,which can reduce the drug leakage.While in the buffer,the drug can be released more completely.MTT assay revealed that the cytotoxicity of lipid nanoparticles increased slightly after enteric coating,but it is still safe in the concentration of 100 g/ml.In cellular uptake experiments,after flocculation in artificial gastric juice and redispersion in artificial intestinal juice,ordinary nanoparticles were absorbed saturatedly within 1 h,and the absorption does no longer increase,compared to ordinary nanoparticle dispersion without flocculation and dispersion,which fluorescence intensity is weaker.The results proved that the ability of cells to ingest ordinary nanoparticles flocculing in artificial gastric juice declined.This may be related to the difficulty of dispersing after flocculation in acid.And the dispersion of enteric coating nanoparticles after flocculation in acid and in buffer shows not only the same fluorescence intensity as odinary nanoparticles without flocculating and dispersion but even stronger,which may be deduced that enteric coating was effective to against the pH variation which caused the unstability of nanoparticles.MDCK cells monolayers were constructed to study the transmembrane transport process of solid lipid nanoparticles.It can be learned that PAPP of enteric coating nanoparticles after flocculation and dispersion were about 27.09 cm/s,and ordinary nanoparticles is only 5.07 cm/s.The coating nanoparticles cross the cell more easily and the throughput is higher than ordinary nanoparticles.All the results showed that coated nanoparticles could be more stable when passing through the gastrointestinal environment,which was beneficial forthe uptake and transport of nanoparticles by intestinal epithelial cells.In conclusion,the enteric coating nanoparticles do have the effect of protecting nanoparticles fromaccumulation,deposition and being eroded by acid,which enable to block drug leakage and protect the gastrointestinal environment.At the same time,the uptake of nanoparticles and the bioavailability of drugs was improved.